Nitric oxide hypoxia-ischemia

Hypoxia is an integral part of ischemia and plays a vital role in its pathophysiology. Hypoxia inducible factor (HIF-1) mediates transcription of several genes. Activation of HIF-1 also stimulates the production of VEGF, erythropoietin, bFGF, and other factors associated with neovascularization (Semenza, 2000 Maxwell and RatcHffe, 2002 Vincent et al., 2002). Another potential factor for neovascularization is adenosine, a neuromodulator that can act on specific receptors (putatively A2A and A2B receptors) on the endothelial cells, and through nitric oxide mediation it can stimulate cell migration and tube formation (Lutty and Mcleod, 2003). 

While currently novel, the idea that cerebral as well as peripheral metabolism can be actively altered during hypoxia-ischemia appears to be well founded. The mechanisms by which reductions in metabolism are achieved are presently unknown but at least two vasoactive compounds important in the hemodynamic response to hypoxia (namely nitric oxide and adenosine) are also able to elicit metabolic alterations and are thus prime candidates for mediation of metabolic adaptations. 

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